The JAK2-Akt-glycogen synthase kinase-3β signaling pathway is involved in toll-like receptor 2-induced monocyte chemoattractant protein-1 regulation
| Autor: | Tae-Whal Jeong, Suk-Hwan Baek, Dae-Weon Park, Yoe-Sik Bae, H. S. Lee, Byung-Rho Chin, Jin-Sik Kim |
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| Rok vydání: | 2011 |
| Předmět: |
Cancer Research
Morpholines monocyte chemoattractant protein-1 janus kinase 2 Biochemistry Article Glycogen Synthase Kinase 3 Lipopeptides Mice GSK-3 Cell Line Tumor Genetics Animals Phosphorylation glycogen synthase kinase-3 β Glycogen synthase Molecular Biology Protein kinase B GSK3B PI3K/AKT/mTOR pathway Chemokine CCL2 Mice Knockout Janus kinase 2 Glycogen Synthase Kinase 3 beta biology Akt Toll-Like Receptor 2 Cell biology Oncology Chromones Myeloid Differentiation Factor 88 biology.protein Cancer research Molecular Medicine toll-like receptor Signal transduction Lithium Chloride Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Molecular Medicine Reports |
| ISSN: | 1791-3004 |
| Popis: | Monocyte chemoattractant protein-1 (MCP-1) is an essential cytokine for the migration of monocytes into vessels, and is also involved in the pathogenesis of atherosclerosis. In this study, we investigated the importance of janus kinase 2 (JAK2) and the function of the Akt and glycogen synthase kinase-3β (GSK3β) pathway in toll-like receptor (TLR2)-mediated MCP-1 expression. The TLR2 agonist, Pam3CSK4, induced MCP-1 expression in the Raw264.7 cell line. The induction of MCP-1 was seen in the bone marrow-derived macrophages of wild-type mice but not in TLR2 knockout mice. The TLR2-mediated MCP-1 induction was myeloid differentiation primary response gene 88 (MyD88)-independent. By contrast, the inactivation of JAK2 attenuated TLR2-mediated MCP-1 expression. The JAK inhibitor suppressed the phosphorylation of GSK3β as well as Akt by Pam3CSK4 stimulation. While the inactivation of Akt by LY294002 suppressed TLR2-mediated MCP-1 induction, the inactivation of GSK3β by LiCl potentiated TLR2-mediated MCP-1 induction. Furthermore, Akt inhibitor suppressed TLR2-mediated phosphorylation of GSK3β. Taken together, these results suggest that a MyD88-independent pathway exists in TLR2 signaling; the JAK2-Akt-GSK3β pathway is a novel MyD88-independent pathway for MCP-1 induction. |
| Databáze: | OpenAIRE |
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